Transdermal dosage form comprising an active agent and a salt and a free-base form of an adverse agent

a technology of adverse agent and active agent, which is applied in the direction of biocide, bandages, drug compositions, etc., can solve the problems that the careful disposal of used dosage forms might not be completely effective for preventing abuse, and the amount of active agent remaining in the dosage form is susceptible to intentional or inadvertent abuse or misuse, and the effect of inhibiting the euphoric effect of the opioid

Inactive Publication Date: 2008-01-24
PURDUE PHARMA LP
View PDF67 Cites 82 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0011] In another embodiment, the present invention is directed to transdermal dosage forms comprising an active agent, a pharmaceutically acceptable salt of an adverse agent and an adverse agent in the form of a free base, in an amount sufficient to inhibit at least one biological effect of the active agent.
[0012] In another embodiment, the present invention is directed to a transdermal dosage form comprising an analgesically effective amount of an opioid or a pharmaceutically acceptable salt thereof (hereinafter “Opioid”), an opioid antagonist in the form of a free base (hereinafter “Antagonist Free Base”),

Problems solved by technology

However, many dosage forms, and particularly those intended for timed and sustained release of active agents, contain large amounts of active agents, often in an amount that is many times the actual dose absorbed or delivered.
Thus, there is often a significant amount of the active agent remaining in the dosage form after use and removal of the device by the user.
Both the unused dosage form and the portion of active agent that remains in the dosage form after use are potentially subject to intentional or inadvertent abuse or misuse, particularly if the active agent is a narcotic

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Transdermal dosage form comprising an active agent and a salt and a free-base form of an adverse agent
  • Transdermal dosage form comprising an active agent and a salt and a free-base form of an adverse agent
  • Transdermal dosage form comprising an active agent and a salt and a free-base form of an adverse agent

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0088] A transdermal dosage form according to FIG. 3A was prepared, with the first adhesive layer comprising 15 mg / cm2 fentanyl free base in adhesive. The second adhesive layer comprised 15 mg / cm2 nalmefene HCl in adhesive. Several 2 cm2 portions of the device were die-cut, the protective liner removed, the portions immobilized and added to testing vessels. The amount of fentanyl free base and of nalmefene HCl extractable from the device (and thus potentially available for abuse) in some cases contained within the transdermal disposal device, was determined through extraction using the following solvents: phosphate-buffered saline (“PBS”), alcohol / water mixture and ethyl ether. 15 mL aliquots of solvent were used in each extraction. The PBS solution was prepared by combining equal amounts of a 0.1M phosphate buffer (pH 6.5) and a 0.5M solution of sodium chloride. The alcohol / water mixture was prepared by mixing 75 parts absolute ethanol with 25 parts water.

[0089] The test sample vi...

example 2

[0092] A transdermal dosage form according to FIG. 3A was prepared, with the first adhesive layer comprising 15 mg / cm2 fentanyl free base in adhesive. The second adhesive layer comprised approximately equal amounts of naltrexone and nalmefene HCl in adhesive, at a total loading of 15 mg / cm2. Several 2 cm2 portions of the device were die-cut, the protective liner removed, the portions immobilized and added to testing vessels. The amount of fentanyl free base, nalmefene HCl and naltrexone extractable from the device (and thus potentially available for abuse) in some cases contained within the transdermal disposal system, was determined through extraction using the following solvents: PBS, alcohol / water mixture and diethyl ether. 15 mL aliquots of solvent were used in each extraction. The PBS solution was prepared by combining equal amounts of a 0.1M phosphate buffer (pH 6.5) and a 0.5M solution of sodium chloride. The alcohol / water mixture was prepared by mixing 75 parts absolute etha...

example 3

[0097] Table 6 shows the data obtained after 30 minutes for the patches tested in Examples 1 and 2.

TABLE 6EXTRACTION DATA AT 30 MINUTESPBSEthanol / WaterDiethyl Ether(μg)(μg)(μg)Example 1Fentanyl25640974339Nalmefene HCl15834353Fentanyl:Antagonist17.04.912.3RatioExample 2Fentanyl30645133646Nalmefene HCl357211346Naltrexone38735534Fentanyl:Antagonist4.23.11.9Ratio

The ratios recited are the amount of extracted fentanyl divided by the total amount of extracted agonist.

[0098] As shown in Table 6, extraction of an illustrative transdermal dosage form of the invention results in a mixture of an Opioid and Antagonist. The ratio of extracted Opioid to total extracted Antagonist in a patch having an Opioid, Antagonist Free Base and Antagonist Salt is lower than that of a transdermal device having only an Opioid and Angonist Salt. Because extraction of the illustrative transdermal dosage form provides a lower ratio of extracted Opioid to extracted Antagonists relative to a device that contain...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
Massaaaaaaaaaa
Massaaaaaaaaaa
Massaaaaaaaaaa
Login to view more

Abstract

This invention relates to a tamper-resistant transdermal dosage form comprising an active agent, such as an opioid, or a pharmaceutically acceptable salt thereof, a free base of an adverse agent, such as an opioid antagonist, and a pharmaceutically acceptable salt of an adverse agent, such as an opioid antagonist. The transdermal dosage form allows an effective amount of the active agent, or a pharmaceutically acceptable salt thereof, to be transdermally administered to an animal. The invention further relates to methods for treating or preventing pain in an animal comprising contacting the skin of an animal in need thereof with the transdermal dosage form of the invention for an amount of time sufficient to treat or prevent pain.

Description

1. FIELD OF THE INVENTION [0001] The present invention relates to transdermal dosage forms useful for preventing or discouraging the abuse of an active pharmaceutical agent, such as an opioid. The present invention further relates to tamper-resistant transdermal dosage forms comprising an active pharmaceutical agent or a pharmaceutically acceptable salt thereof, and an adverse agent of the active pharmaceutical agent, the adverse agent comprising both a free base adverse agent and a pharmaceutically acceptable salt of the adverse agent. In particular, the present invention relates to tamper-resistant transdermal dosage forms comprising an opioid or a pharmaceutically acceptable salt thereof, a free-base opioid antagonist, and a pharmaceutically acceptable salt of an opioid antagonist. 2. BACKGROUND OF THE INVENTION [0002] Transdermal dosage forms are convenient for delivering many different therapeutically effective agents, including but not limited to analgesics, such as opioid ana...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): A61K9/70A61K31/4184A61K31/439A61K31/44A61K31/4439A61P25/04A61K31/445A61K31/4535A61K31/485A61K31/5377
CPCA61K9/7061A61K9/7069A61K9/7084A61K31/4184A61K31/439A61K31/5377A61K31/4439A61K31/445A61K31/4535A61K31/485A61K31/44A61P25/04
Inventor SHEVCHUK, IHORREIDENBERG, BRUCE
Owner PURDUE PHARMA LP
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap